Intracranial cerebral aneurysms are most commonly found as arterial saccular dilatations located at points where parent arteries bifurcate into branch vessels. The incidence of these lesions in human autopsy studies is approximately 5%. Most aneurysms remain asymptomatic due to a low rupture rate of 0.5 to 4% per year depending upon their size, shape, and location (average rate of rupture 1%). The mortality rate after rupture is between 30 and 60% if no treatment is administered. Of the remaining patients, outcome depends upon (1) the patient's neurologic condition when he/she presents for care and (2) the complexity of aneurysm treatment.
Current treatment for both ruptured and unruptured aneurysms includes surgical clipping (exovascular therapy) and catheter based intervention (endovascular therapy). The latter includes the placement of platinum coils or liquid gels into the aneurysm to arrest blood flow within the aneurysm sac and induce thrombosis of the lesion and its subsequent exclusion from the native circulation and/or placement of stent like devices across the aneurysm neck to achieve similar results. Some aneurysms are more amenable to one therapy or the other. Randomized controlled studies have shown that when aneurysms are judged to be good candidates for either therapy, endovascular therapy leads to better neurologic outcomes.
The primary downsides to endovascular aneurysm therapy are the risk of aneurysm recurrence and subsequent lesion rupture or re-rupture. While recurrence is possible when any aneurysm is treated endovascularly, the increased likelihood of such an event is directly proportional to increased aneurysm size, increase volume of pre-therapy intra-aneurysmal thrombus, and low fundus to neck ratio (fundal diameter primarily in the non-Z plane divided by the aneurysm neck diameter). These different criteria affect the surgeon's ability to densely fill the aneurysm with coil material so that coil compaction into the aneurysm's dome is limited. Such compaction is caused by a combination of arterial blood pressure pulsations which force the coil loops to densely collapse on one another thus opening up new space in the aneurysm dome and by intra-aneurysmal thrombolysis which reduces the ability for thrombus within the aneurysm to organize and support the coil mass against collapse into the aneurysm dome.
In an attempt to reduce the incidence of aneurysm recurrence following endovascular coiling, manufacturers have made several attempts to modify the platinum coil surface, coil shape/geometry, and coil stiffness. These modifications all seek to induce the holy grail of endovascular aneurysm therapy, maximization of coil pack density within the aneurysm (close to or greater than 35% of total aneurysm volume filled with coil material) and subsequent exclusion of the aneurysm neck from the native circulation and parent vessels by the induction of an endothelial layer that covers the interface between the coil material in the aneurysm neck and the parent vessel lumen and arterial blood flow. It is the growth of this endothelial layer that seals the aneurysm off from the normal arterial blood flow thus eliminating the risk of aneurysm recurrence.
While all coil manufacturers have altered their product's geometry and stiffness in an attempt to maximize coil density within the aneurysm fundus, only two manufacturers have altered their coil surfaces and studied the consequences of such alterations on aneurysm recurrence and endothelialization. Reinges et al. (Bare, Bio-Active and Hydrogel-Coated Coils for Endovascular Treatment of Experimentally Induced Aneurysms: Long-Term Histological and Scanning Electron Microscopy Results. Interventional Radiology, 2010. 16(2): p. 139-150) studied the different outcomes after coiling of experimental aneurysm using, unmodified platinum coils, hydrogel coated coils (HydroCoil, Microvention Therapeutics), and bioactive coils coated with PLGA copolymers (Matrix Coil, Boston Scientific, Fremont, Calif.). The premise behind hydrogel coating is that once the coil is inserted into the aneurysm the hydrogel swells, thus increasing the density of material within the aneurysm fundus and increasing the surface area of material at the neck of the aneurysm. These two effects of the coating presumably facilitate improved endothelial growth across the aneurysm neck and subsequent aneurysm exclusion from the native circulation. The premise behind the PLGA coating of bioactive coils is for the PLGA to produce an inflammatory reaction within the aneurysm and at the neck of the aneurysm thus enhancing clot organization and maturation and accelerating neointimal proliferation. The authors found that PLGA provided no benefits compared to bare platinum coils. Hydrogel coils increased the likelihood of intraneurysmal fibrosis along with instances of neoendothelial proliferation and endothelial spanning of tissue from one coil loop to another leading to neck coverage. Murayama et al. (Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: concepts and preliminary results in swine models. Neurosurgery, 1997. 40(6): p. 1233-43; discussion 1243-4) also looked to alter platinum coils using ion implantation and protein coating with fibronectin. They found greater fibrous coverage of the aneurysm necks in the modified coils group compared to the bare platinum treated animals. These experimental results have been partially confirmed by clinical studies. Piotin et al. (Intracranial Aneurysms Coiling With Matrix: Immediate Results in 152 Patients and Midterm Anatomic Follow-Up From 115 Patients. Stroke, 2009. 40(1): p. 321-323) found that Matrix coils provided no improvement in aneurysm recanalization rates compared to bare platinum coils.
Once an aneurysm is filled with coils, the influx of pulsating blood is reduced as hemodynamic pressure is distributed and absorbed by the coil mass. Intraneurysmal blood flow becomes turbulent and the process of coagulation can begin (Piotin, M., et al., Intracranial Aneurysms Coiling with Matrix: Immediate Results in 152 Patients and Midterm Anatomic Follow-Up From 115 Patients. Stroke, 2009. 40(1): p. 321-323). Histologic studies have shown that following coil placement in an aneurysm dome, platelets and fibrin deposit on the coil's loops. Over time the fibrin clot organizes and granulation tissue forms between the coil loops thus stabilizing them. This tissue forms a matrix over which neoendothelial cells, which emerge from the surrounding healthy vessel wall, can gradually grow from the periphery to eventually cover the portion of the coils exposed to the arterial blood flow in the parent vessel's lumen. In the ideal situation, this neoendothelial layer effectively isolates the aneurysm from the arterial blood flow eliminating the risk of subsequent aneurysm recanalization, recurrence, and rupture. However, the rate at which a complete neoendothelial layer forms is currently unknown. Literature suggests that after 5 days of coil deposition a thrombus consisting of erythrocytes and fibrin are found throughout the dome. Within 2 weeks foamy macrophages are found near the coils and by 270 days scar formation with vascularized connective tissue surrounds the coils and fills the fundus while endothelial cells seal the aneurysm neck. It is the surgeon's hope that this process can occur as quickly and reliably as possible since an ideal outcome is contingent upon the completion of this process.
Histologic findings following the use of hydrogel coated coils suggest that this material might enhance neoendothelial sealing of the aneurysm by promoting thrombosis through a more dense aneurysm fill and by presenting a greater surface are at the neck over which neoendothelial cells can sprout and spread to form a contiguous membrane. While the use of hydrogel coatings may seem attractive, a subset of patients who underwent HydroCoil implantation have developed delayed aseptic meningitis, intraparenchymal cyst formation, and hydrocephalus. It is unclear whether or not higher rates of aneurysm occlusion justify such potential complications.